The excessive prevalence of end stage renal disease among African Americans is related to the high incidence of essential hypertension (EH) and non-insulin dependent diabetes mellitus (NIDDM). In African Americans, as well as whites, both EH and NIDDM are associated with insulin resistance. An increase in activity of the red cell sodium-lithium counter transport (SLC) is observed in whites with EH. Insulin dependent diabetics with nephropathy also have increased activity of SLC. Within young African Americans, we have detected increased SLC activity in association with insulin resistance. Also, increased SLC activity in young adult African American is associated with greater rates of urinary albumin excretion (UAE) and an atherogenic lipid profile, suggesting that the vascular disease may be underway prior to expression of clinical EH or NIDDM. Our data suggest that insulin resistance and SLC could be predictive of renal injury, and could modulate the expression of NIDDM and EH. Our overall hypothesis is: Insulin resistance and high SLC activity increase UAE and increase blood pressure (BP) in African Americans. In this project we will conduct a prospective longitudinal study to investigate the contribution of insulin resistance and SLC to the risk for nephropathy in African American men and women. The study sample will consist of normotensive young adults and young adults with borderline hypertension. This sample has already bee characterized for the parameters proposed in the longitudinal study. Our aims are to 1) Determine the change in insulin sensitivity and detect parameters associated with a change in insulin sensitivity, including BP, body mass, central adiposity, and plasma lipids; 2) Determine if SLC changes, and parameters associated with SLC change; 3) Examine longitudinally the change in UAE and the change in BP; 4) Identify the determinants of increasing UAE and increasing BP in African american men and women, and characterize the risk for nephropathy. Currently available data, which address determinants of renal disease in EH and NIDDM are based on cross-sectional studies. Data from this project would provide a longitudinal dimension, thereby providing new insights to mechanisms underlying EH and NIDDm. Results of this investigation could also contribute to the development of strategies for prevention of the excessive renal disease in African Americans with EH and NIDDM.